Extending the Clinical Horizons of Mucosal Bacterial Vaccines: Current Evidence and Future Prospects

Abstract

Antibiotics remain the mainstay of treatment for infectious diseases, but the growing frequency of antibiotic resistance represents a major concern for healthcare worldwide. The use of antibiotics in recurrent infections raises other issues, such as their limitations for treating diverse microorganisms, deleterious effects on the microbiota of the patient and potential adverse effects. In recent years, progress has been made towards the development of novel polybacterial vaccines administered via the mucosal route. These drugs target both the innate and adaptive immune systems, at the actual point of entry of most pathogens. In addition to boosting immune responses, mucosal bacterial vaccines have an intriguing immunomodulatory activity that does not compromise their efficacy against infectious agents. We review here the current clinical evidence concerning the efficacy and safety of these mucosal vaccines for the prevention and treatment of recurrent infection. We also provide an overview completing the landscape of the potential clinical uses of these active biological agents.

MV140, a sublingual polyvalent bacterial preparation to treat recurrent urinary tract infections, licenses human dendritic cells for generating Th1, Th17, and IL-10 responses via Syk and MyD88

“…Currently, antibiotics are still the main therapeutic option used for the treatment of RUTIs. 1,2 However, the overuse of antibiotics in humans has been associated with the increase in antibiotic-resistant infections, which represents a major public health concern worldwide that menaces the effective prevention and treatment of a wide range of infections caused by bacteria, parasites, viruses and fungi. 20,21 Other negative factors associated to the overuse of antibiotics include horizontal gene transfer, limitation in terms of diversity of action spectra and deleterious effects in microbiota, which enhance pathogen invasion and subsequent fungal superinfections.…”

“…Among these alternatives, the development of mucosal bacterial vaccines has received a lot of attention over the last years. 1 Different studies suggest that formulations based on PBPs of inactivated whole cells represent suitable vaccines able to induce more potent and effective immune responses than bacterial lysates. 22,23 In contrast to oral administration, sublingual immunization protects the PBPs from gastrointestinal degradation and induces strong and durable immune responses not only locally but also in peripheral lymphoid organs and distant mucosal tissues, such as the urinary tract.…”

“…3 The pathogen most frequently isolated from patients with UTIs is Escherichia coli (80% of infections), followed by Staphylococcus saprophyticus, Klebsiella pneumoniae, Proteus spp and Enterococcus spp. 1,3,4 Antibiotics remain the mainstay of treatment for RUTIs, 1 but their overuse is associated with antibiotic-resistant infections and deleterious effects in the microbiota. [5][6][7] Therefore, there is an urgent need for the development of new alternative approaches to treat patients suffering from recurrent infections.…”

“…[5][6][7] Therefore, there is an urgent need for the development of new alternative approaches to treat patients suffering from recurrent infections. 1 Different types of mucosal bacterial vaccines have gained a lot of attention for the treatment of RUTIs over the last years. Bacterial vaccines may contain soluble antigens (bacterial components or lysates) 8,9 or inactivated whole bacteria from one or more species or strains.…”

“…[10][11][12] Mucosal bacterial vaccines for RUTIs were initially administrated orally, but more recently the sublingual delivery route has been also assayed. 1,8,12 The sublingual epithelium contains a dense network of dendritic cells (DCs) that play an essential role in linking innate and adaptive immune responses. 13,14 DCs are equipped with a wide battery of pattern recognition receptors (PRRs) such as toll-like receptors (TLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs) as sensors of pathogen-associated molecular patterns (PAMPs).…”